Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01185 (vasopressin)
 23,126 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incubation of hepatocytes with the protein kinase C activator and tumour promoter 4 beta-phorbol 12 beta-myristate 13 alpha-acetate (PMA) produced a time- and concentration-dependent inactivation of glycogen synthase, but no change in phosphorylase. The same rate and extent of inactivation occurred in hepatocytes depleted of Ca2+ by treatment with the Ca2+ chelator EGTA. When hepatocytes were treated with the Ca2+-mobilizing hormone vasopressin (10 nM), the rate of glycogen synthase inactivation was similar to that observed with PMA (1 microM). Depletion of intracellular Ca2+ stores with EGTA abolished the ability of vasopressin to mobilize Ca2+ and activate phosphorylase without abolishing its ability to inactivate glycogen synthase and increase 1,2-diacylglycerol (DAG), the endogenous activator of protein kinase C. Protein kinase C, either in membranes or after partial purification, was shown to be activated in vitro by PMA in the presence of very low concentrations of Ca2+. Exogenous phospholipase C from Clostridium perfringens, at low concentrations, inactivated glycogen synthase and increased DAG without affecting cell Ca2+ or phosphorylase. It is proposed that the inactivation of glycogen synthase elicited by the Ca2+-mobilizing hormones is due, at least in part, to generation of DAG and activation of protein kinase C.
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PMID:Mechanism of hepatic glycogen synthase inactivation induced by Ca2+-mobilizing hormones. Studies using phospholipase C and phorbol myristate acetate. 309 47

Vasopressin caused a 40% inhibition of 45Ca uptake after the addition of 0.1 mM-45Ca2+ to Ca2+-deprived hepatocytes. At 1.3 mM-45Ca2+, vasopressin and ionophore A23187 each caused a 10% inhibition of 45Ca2+ uptake, whereas La3+ increased the rate of 45Ca2+ uptake by Ca2+-deprived cells. Under steady-state conditions at 1.3 mM extracellular Ca2+ (Ca2+o), vasopressin and La3+ each increased the rate of 45Ca2+ exchange. The concentrations of vasopressin that gave half-maximal stimulation of 45Ca2+ exchange and glycogen phosphorylase activity were similar. At 0.1 mM-Ca2+o, La3+ increased, but vasopressin did not alter, the rate of 45Ca2+ exchange. The results of experiments performed with EGTA or A23187 or by subcellular fractionation indicate that the Ca2+ taken up by hepatocytes in the presence of La3+ is located within the cell. The addition of 1.3 mM-Ca2+o to Ca2+-deprived cells caused increases of approx. 50% in the concentration of free Ca2+ in the cytoplasm [( Ca2+]i) and in glycogen phosphorylase activity. Much larger increases in these parameters were observed in the presence of vasopressin or ionophore A23187. In contrast with vasopressin, La3+ did not cause a detectable increase in glycogen phosphorylase activity or in [Ca2+]i. It is concluded that an increase in plasma membrane Ca2+ inflow does not by itself increase [Ca2+]i, and hence that the ability of vasopressin to maintain increased [Ca2+]i over a period of time is dependent on inhibition of the intracellular removal of Ca2+.
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PMID:Effects of vasopressin and La3+ on plasma-membrane Ca2+ inflow and Ca2+ disposition in isolated hepatocytes. Evidence that vasopressin inhibits Ca2+ disposition. 309 75

1. In isolated hepatocytes NaF increased the rate of 45Ca2+ exchange, the cytoplasmic free Ca2+ concentration ([Ca2+]i) (monitored by using quin2), and the activity of glycogen phosphorylase a in a Ca2+-dependent manner. 2. In cells previously incubated in the absence of extracellular Ca2+(Ca2+o), NaF caused a pronounced enhancement in the increases in the activity of glycogen phosphorylase and in [Ca2+]i observed when Ca2+ was subsequently added. The effect of NaF on glycogen phosphorylase activity was inhibited by verapamil and deferoxamine, and was potentiated by AlCl3. 3. The actions of NaF were associated with (a) increases in [3H]inositol polyphosphates, which were slower in onset and about half the magnitude of those induced by vasopressin, in hepatocytes labelled with [3H]inositol, and (b) enhanced rates of O2 utilization and decreased concentrations of ATP. The latter effects were not potentiated by AlCl3. 4. Preincubation of hepatocytes with vasopressin in the absence of added Ca2+o for times up to 30 min did not diminish the ability of a subsequent addition of extracellular Ca2+ to activate glycogen phosphorylase. 5. 12-O-Tetradecanoylphorbol 13-acetate had little effect on 45Ca2+ exchange and did not enhance the activation by Ca2+o of phosphorylase in hepatocytes incubated in the absence of Ca2+o. 6. On the basis of the observation that AlF4- activates GTP-binding regulatory proteins [Sternweiss & Gilman (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 4888-4891], it is concluded that the present results provide evidence for the function of a GTP-binding regulatory protein in the mechanism by which hormones stimulate plasma-membrane Ca2+ inflow in the liver cell, and indicate that an increase in [Ca2+]i and the activation of protein kinase C are not part of this mechanism.
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PMID:The stimulation by sodium fluoride of plasma-membrane Ca2+ inflow in isolated hepatocytes. Evidence that a GTP-binding regulatory protein is involved in the hormonal stimulation of Ca2+ inflow. 311 43

Glutamine stimulated glycogen synthesis and lactate production in hepatocytes from overnight-fasted normal and diabetic rats. The effect, which was half-maximal with about 3 mM-glutamine, depended on glucose concentration and was maximal below 10 mM-glucose. beta-2-Aminobicyclo[2.2.1.]heptane-2-carboxylic acid, an analogue of leucine, stimulated glutaminase flux, but inhibited the stimulation of glycogen synthesis by glutamine. Various purine analogues and inhibitors of purine synthesis were found to inhibit glycogen synthesis from glucose, but they did not abolish the stimulatory effect of glutamine on glycogen synthesis. The correlation between the rate of glycogen synthesis and synthase activity suggested that the stimulation of glycogen synthesis by glutamine depended solely on the activation of glycogen synthase. This activation of synthase was not due to a change in total synthase, nor was it caused by a faster inactivation of glycogen phosphorylase, as was the case after glucose. It could, however, result from a stimulation of synthase phosphatase, since, after the addition of 1 nM-glucagon or 10 nM-vasopressin, glutamine did not interfere with the inactivation of synthase, but did promote its subsequent re-activation. Glutamine was also found to inhibit ketone-body production and to stimulate lipogenesis.
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PMID:Stimulation of glycogen synthesis and lipogenesis by glutamine in isolated rat hepatocytes. 312 12

In hepatocytes pre-labelled with [3H]glycerol, compound R59022 (6-[2-(4-[(4-fluorophenyl)phenylmethylene]-1-piperidinyl)ethyl]-7- methyl-5H-thiazolo[3,2-alpha]pyrimidin-5-one) and 2-bromooctanoate each increased the amount of radioactivity in diacylglycerols. R59022 mimicked the actions of 12-O-tetradecanoylphorbol 13-acetate in completely abolishing the activation by adrenaline (but not that by vasopressin or glucagon) of glycogen phosphorylase a, and in decreasing the activity of glycogen synthetase. Exogenous dioctanoylglycerol caused a small inhibition of adrenaline-stimulated phosphorylase activity. The concentration of R59022 which gave half-maximal inhibition of adrenaline-stimulated phosphorylase activity was 15 microM. Maximal inhibition was observed within 2 min of addition of R59022. 2-Bromooctanoate activated phosphorylase by a process independent of changes in cyclic AMP and Ca2+, and decreased glycogen synthetase. It is concluded that in hepatocytes (i) diacylglycerols which accumulate as a result of the inhibition of diacylglycerol kinase by R59022 activate protein kinase C and (ii) 2-bromooctanoate increases diacylglycerols but also has other effects on hepatocyte metabolism.
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PMID:Effects of inhibitors of diacylglycerol metabolism on protein kinase C-mediated responses in hepatocytes. 313 Aug 94

The regulation of glycogen synthase by Ca2+-mobilizing hormones was studied by using rat liver parenchymal cells in primary culture. Long-term exposure of hepatocytes to 4 beta-phorbol 12-myristate 13-acetate (TPA) resulted in a decrease in vasopressin or ATP inhibition of glycogen synthesis and glycogen synthase activity, without any change in the activation of glycogen phosphorylase. In contrast, treatment with TPA did not diminish the effects of glucagon, isoprenaline or A23187 on glycogen synthase or phosphorylase. TPA treatment for 18 h did not change specific [3H]vasopressin binding, but abolished protein kinase C activity in a concentration-dependent manner. The effects of TPA to decrease protein kinase C activity and to reverse the inactivation of glycogen synthase by vasopressin were well correlated and were mimicked by mezerein, but not by 4 alpha-phorbol. However, 1 microM-TPA totally inhibited protein kinase C activity, but reversed only 60% of the vasopressin effect on glycogen synthase. It is therefore concluded that Ca2+-mobilizing hormones inhibit glycogen synthase partly, but not wholly, through a mechanism involving protein kinase C.
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PMID:The role of protein kinase C in the inactivation of hepatic glycogen synthase by calcium-mobilizing agonists. 313 12

The ability of angiotensin II to down-regulate its receptor was tested on rat hepatocytes in primary culture for 4 h. Angiotensin II treatment decreased [3H]angiotensin II specific binding in a concentration- and time-dependent manner. The effect was maximum with 1 microM angiotensin II and after 2 h. There was a decrease in the maximum number of binding sites (56% of control) with no significant effect on the apparent dissociation constant. The down-regulation was blocked by the angiotensin II antagonist [Val4,Ile7]angiotensin III and was not induced by other hormones (e.g. vasopressin, norepinephrine, or glucagon) or by 4 beta-phorbol 12 beta-myristate 13 alpha-acetate or A23187 ionophore. The decrease in angiotensin II receptors resulted in correlated decreases in the potency of angiotensin II to activate phosphorylase or lower glucagon-induced cAMP accumulation. However, high concentrations of the agonist were still able to elicit maximal responses in both parameters. Down-regulation of the receptor was not dependent upon active Gi, since it was still observed after ADP-ribosylation and inactivation of Gi by pertussis toxin. The above results indicate that the down-regulation of the hepatic angiotensin II receptor induced by its agonist is homologous and does not involve Gi, Ca2+, or protein kinase C. The correlation of receptor loss with decreases in the potency of angiotensin to activate phosphorylase and inhibit glucagon-induced cAMP accumulation is consistent with the idea that a single receptor population regulates two different messengers, i.e. calcium and cAMP.
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PMID:Agonist-induced down-regulation of the angiotensin II receptor in primary cultures of rat hepatocytes. 313 62

Treatment of isolated hepatocytes with F- produced a concentration-dependent activation of phosphorylase, efflux of Ca2+, rise in [Ca2+]i, increase in Ins 1,4,5-P3 levels, decrease in PI-4,5-P2 levels, and increase in DAG levels. The levels of intracellular cAMP were decreased by NaF. The effects of NaF were potentiated by AlCl3. This potentiation was abolished by the Al3+ chelator deferoxamine. These results illustrate that AlF4- can mimic the effects of Ca2+-mobilizing hormones in hepatocytes and suggest that the coupling of the receptors for these hormones to the hydrolysis of PI-4,5-P2 is through a guanine nucleotide-binding regulatory protein. This is because AlF4- is known to modulate the activity of other guanine nucleotide regulatory proteins (Gi, Gs, and transducin). Calcium-sensitive inositide release in a purified rat liver plasma membrane preparation was increased by calcium-mobilizing hormones in the presence of guanine nucleotides. Vasopressin-stimulated inositide release was evident in the presence of GTP or GTP gamma S. The guanine nucleotide and hormonal stimulation was evident on both inositide production and PI 4,5-P2 degradation. Treatment of plasma membranes with cholera toxin or islet activating protein or prior injection of animals with islet activating protein did not affect stimulation of inositide release by GTP gamma S or GTP gamma S plus vasopressin. The results suggest that calcium-mobilizing hormones stimulate polyphosphoinositide breakdown in rat liver plasma membranes through a novel guanine nucleotide binding protein. The GTPase activity of rat liver plasma membranes was stimulated 20% by 10(-8) M vasopressin. The vasopressin-stimulated GTPase activity was not inhibited in plasma membranes that had been ADP-ribosylated with either cholera toxin or pertussis toxin. When membranes that had been solubilized after preincubation with [3H]vasopressin were subjected to sucrose gradient centrifugation, most of the protein-bound [3H]vasopressin migrated as a single band, also, there was a GTPase activity that migrated with the bound [3H]vasopressin. This peak of bound [3H]vasopressin was decreased 90% when the sucrose gradient centrifugation was run in the presence of 10 M GTP gamma S. Direct evidence that a GTP-binding protein was present in the [3H]vasopressin peak was obtained by the immuno-detection of a 35 kDa beta subunit of a GTP-binding protein and a 40 kDa alpha subunit. These results support the conclusion that liver plasma membranes contain a GTP-binding protein that can complex with the vasopressin receptor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Role of guanine nucleotide regulatory proteins and inositol phosphates in the hormone induced mobilization of hepatocyte calcium. 314 79

The effects of neomycin on Ca2+ fluxes and inositol polyphosphates in hepatocytes were investigated since it has been proposed that this antibiotic inhibits inositol 1,4,5-triphosphate formation in fibroblasts [D. H. Carney, D. L. Scott, E. A. Gordon and E. F. LaBelle, Cell 42, 479 (1985)]. In hepatocytes incubated at 1.3 mM extracellular Ca2+ (Ca2+o) neomycin (2 mM) inhibited 45Ca2+ exchange both in the presence or absence of vasopressin. At 1.3 mM Ca2+o, but not at higher concentrations of Ca2+o, the antibiotic (2 mM) inhibited the increase in glycogen phosphorylase a activity observed at late but not at early times after addition of vasopressin. The antibiotic also inhibited the increase in phosphorylase activity caused by the subsequent addition of 1.3 mM Ca2+o to cells previously incubated in the presence of vasopressin and in the absence of added Ca2+o. The concentration of the antibiotic (2 mM) which gave half-maximal inhibition of phosphorylase activation by vasopressin had no effect on the activation of phosphorylase by glucagon or the release of Ca2+ from intracellular stores induced by vasopressin. At a concentration of 10 mM, neomycin caused a 50% inhibition of the formation of [3H]inositol polyphosphates induced by vasopressin. It is concluded that neomycin, at concentrations which inhibit phosphoinositide-specific phospholipase C in other types of cells inhibits the inflow of Ca2+ across the plasma membrane but does not inhibit inositol trisphosphate formation in hepatocytes.
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PMID:Evidence that neomycin inhibits plasma membrane Ca2+ inflow in isolated hepatocytes. 325 17

1. In hepatocytes, epidermal growth factor (EFG) (a) increased the rate of 45Ca2+ exchange in cells incubated at 1.3 mM extracellular Ca2+, (b) increased the activity of glycogen phosphorylase a and the intracellular free Ca2+ concentration (measured with quin2) in a process dependent on the concentration of extracellular Ca2+, and (c) enhanced the increase in glycogen phosphorylase activity which follows the addition of Ca2+ to cells previously incubated in the absence of Ca2+. It is concluded that EGF stimulates plasma-membrane Ca2+ inflow. 2. The effects of the combination of EGF and vasopressin on the rate of 45Ca2+ exchange and on the rate of increase in glycogen phosphorylase activity were the same as those of vasopressin alone. 3. The amount of 45Ca2+ released by EGF from internal stores was about 30% of that released by vasopressin. No detectable increase in [3H]inositol mono-, bis- or tris-phosphate was observed after the addition of EGF to cells labelled with myo-[3H]inositol. 4. In hepatocytes isolated from rats treated with pertussis toxin, the effects of EGF and vasopressin on phosphorylase activity (measured at 1.3 mM-Ca2+) and on the rate of Ca2+ inflow (measured with quin2) were markedly decreased compared with those in normal cells. 5. Treatment with pertussis toxin did not impair the ability of vasopressin to release Ca2+ from internal stores, but decreased vasopressin-stimulated [3H]inositol polyphosphate formation by 50%. 6. It is concluded that the mechanism(s) by which vasopressin and EGF stimulate plasma-membrane Ca2+-inflow transporters in hepatocytes involves a GTP-binding regulatory protein sensitive to pertussis toxin, and does not require an increase in the concentration of inositol trisphosphate comparable with that which induces the release of Ca2+ from the endoplasmic reticulum.
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PMID:Evidence that a pertussis-toxin-sensitive substrate is involved in the stimulation by epidermal growth factor and vasopressin of plasma-membrane Ca2+ inflow in hepatocytes. 350 16


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